Large-scale plasma proteomics in population studies offer new avenues to explore non-genetic associations, such as biomarkers for lifestyle and environmental exposure. Moreover, through longitudinal monitoring, they help in characterizing the onset and progression of diseases. Utilizing the SWATH DIA-MS-based proteomic approach with 5-minute chromatographic gradients, we examined the neat plasma proteome of 3,632 participants from the Cooperative Health Research in South Tyrol (CHRIS) study. We present precise protein quantities for 148 highly abundant plasma protein groups. Many of these proteins are challenging to quantify using affinity-based reagents. This set of highly abundant plasma proteins includes immunoglobulins, coagulation factors, metabolic proteins, and components of the innate immune system, such as the complement system. Our findings indicate that, beyond age and sex, the most significant biological variable affecting the plasma proteome was the use of hormonal contraceptives. The signature from this drug class was more pronounced compared to other common medications, which influenced only a subset of the measured proteins and exhibited smaller effect sizes. Notably, Angiotensinogen (AGT) levels were strongly influenced by contraceptive use, suggesting that AGT levels might serve as a potential biomarker for contraceptive usage. Due to its high prevalence, and apparently strong influence, this type of medication should be accounted for in any epidemiological or clinical study of the plasma proteome to avoid spurious findings.